Nanoparticles are spherical particles in sizes ranging from a few nanometers up to 0.1 μm. Polymeric nano-scaled particles of narrow size distribution are commonly formed by controlled precipitation methods or heterogeneous polymerization techniques, e.g., by optimal emulsion or inverse emulsion polymerization methods. Properties of solid materials undergo drastic changes when their dimensions are reduced to the nanometer size regime. It is important to keep in mind that the smaller the particles are, the larger portion of their constituent atoms is located at the surface. Nanoparticles, particularly in sizes below ca. 20 nm, predominantly exhibit surface and interface phenomena that are not observed in bulk materials, e.g., lower melting and boiling points, lower sintering temperature and reduced flow resistance.
In view of their spherical shape and high surface area, nano-scaled particles may provide neat solutions to a variety of problems in materials science, such as composite materials, catalysis, three dimensional structures and photonic uses, and can further be used in biomedical applications such as specific cell labeling and separation, cell growth, affinity chromatography, diagnostics, specific blood purification by hemoperfusion, drug delivery and controlled release (Bockstaller et al., 2003; Hergt et al., 2004; Margel et al., 1999). Each application requires polymeric nanoparticles of different optimal physical and chemical properties. The synthesis and use of numerous types of nano-scaled particles of different surface chemistry, e.g., variety of surface functional groups such as hydroxyl, carboxyl, pyridine, amide, aldehyde and phenyl chloromethyl, have already been described (Margel et al., 1999). Such nanoparticles have been designed for various industrial and medical applications, e.g., enzyme immobilization, oligonucleotide and peptide synthesis, drug delivery, specific cell labeling and separation, medical imaging, biological glues and flame retardant polymers (Bunker et al., 1994; Szymonifka and Chapman, 1995; Margel et al., 1999; WO 2004/045494; Galperin et al., 2007).
Of particular interest are particles with magnetic properties, which are usually used for separation of the particles and/or their conjugates from undesired compounds via a magnetic field. Due to their magnetic properties, these particles have several additional significant applications such as magnetic recording, magnetic sealing, electromagnetic shielding and biomedical applications. Magnetic iron oxide, i.e., magnetite and maghemite, nanoparticles are the main particles that have been investigated for biomedical applications, e.g., magnetic hyperthermia, magnetic drug targeting, magnetic cell separation and as MRI contrast agents (Lacoste et al., 1993; Green-Sadan et al., 2005; Leemputten and Horisberger, 1974; Hergt et al., 2004). Magnetic iron oxides nanoparticles are non-toxic and biodegradable, and have already been approved for clinical use as MRI contrast agents. These nanoparticles are usually prepared by adding to an aqueous solution containing stoichiometric concentrations of ferrous and ferric ions, and a polymeric stabilizer such as dextran, wherein a base, e.g., NaOH or ammonia, is added until basic pH (usually above 8.0) is reached. The obtained coated magnetic iron oxide nanoparticles are than washed by different ways, e.g., by magnetic columns or dialysis. Extensive efforts to synthesize efficient iron oxide magnetic nanoparticles have been carried out in the last several years; however, most of these nanoparticles suffer from major disadvantages such as broad size distribution that is considered to be toxic for in vivo medical applications, iron ions leaching and instability towards agglutination processes.
WO 99/062079 and corresponding EP 1088315B1 of the same Applicant, herewith incorporated by reference in their entirety as if fully disclosed herein, disclose new uniform magnetic gelatin/iron oxide composite nanoparticles, formed by controlled nucleation of iron oxide onto an iron ion chelating polymer, e.g., gelatin, dissolved in an aqueous solution, followed by stepwise growth of thin layers of iron oxide films onto the gelatin/iron oxide nuclei. These magnetic nanoparticles can be prepared in a very narrow size distribution and in sizes ranging from about 10 nm up to 100 nm.